Elagolix for Fertility Enhancement Clinical Trial

Although meta-analyses have not demonstrated an effect of endometriosis on IVF outcomes, most women with endometriosis undergoing IVF have not been diagnosed or treated for their disease. Recent evidence suggests that biomarkers for endometriosis predict IVF failure and miscarriage. Further suppression of endometriosis prior to IVF has been shown to dramatically improve pregnancy rates in unexplained infertility with suspected endometriosis. Elagolix (Orilissa) is a new generation FDA approved orally active GnRHr antagonist that is rapidly reversible, for the treatment of endometriosis and pelvic pain. There have been no studies on the efficacy of elagolix for the treatment of endometriosis-associated infertility. Given the recent study in Fertility and Sterility demonstrating IVF outcome prediction using BCL6 as a biomarker for the presence of endometriosis and subsequent preliminary data showing benefit using surgery and GnRH agonist therapy, there is adequate rationale to examine the use of the orally active, non-peptide compound (elagolix) for estrogen suppression prior to frozen embryo transfer in women who test positive for BCL6 and an associated protein, SIRT1. In this multi-central randomized controlled trial (RCT), the EFFECT Trial, the investigators plan to recruit 100 subjects with prior unexplained IVF failure with positive endometrial BCL6/SIRT1 expression. To qualify all subjects will need to have a preimplantation genetic testing (PGT-A) tested euploid embryo and intentions to undergo frozen embryo transfer. Subjects will be randomized to receive elagolix (200 mg BID) or OCPs for 2 months prior to standardized FET. Primary study outcomes will be pregnancy outcome.

Inclusion criteria

• Anti-Mullerian Hormone (AMH) > 0.5 and < 10
• At least 1 euploid embryo for transfer
• Prior endometrial biopsy showing elevated BCL6 and SIRT1 expression
• Endometrial thickness > 5.9 and < 14 mm

Exclusion criteria

• Uterine fibroids > 4 cm (intramural)
• Polycystic ovary syndrome (Rotterdam criteria)
• Ovarian failure and donor eggs or oocytes
• Positive lupus anticoagulant or positive anti-cardiolipin antibody testing
• Diabetes mellitus (Type I or II)
• Untreated hypothyroidism
• Untreated hyperprolactinemia
• BMI <17 or > 35
• Uncorrected uterine anomaly